Gastro-Esophageal Reflux Disease (GERD) is a chronic heartburn/stomach acidity affliction characterized by a series of symptoms including heartburn, chronic indigestion (dyspepsia), pyrosis, abdominal pain and swelling, epigastric pain, nausea, regurgitation, premature feeling of satiety, acid reflux coughing, vomiting and gas indigestion. GERD is a disease that mainly consists of abnormal refluxing of gastric contents into the esophagus through the lower esophageal sphincter, the lowest portion of the esophagus where it joins the stomach, which prevents the reverse passage of gastric content. The pH of the gastric content is acid, which is why the feeling of heartburn is produced and when it reaches the throat or the mouth, the taste is acidic and bitter, a symptom known as pyrosis. GERD is presently the most prevalent disease in the upper digestive system, and it is very prevalent in the Western world. It is estimated that at least 30 million patients suffer one of the aforementioned forms of GERD in the US each year, with the number rising significantly every year. The greatest incidence occurs in adults over forty. H. pylori is a gram-negative, slowly growing bacteria strain adapted to microaerophilic environments and its presence in the stomach is directly associated with various gastric diseases. 75% of gastric cancers are associated H. pylori infection.
Since Helicobacter pylori (initially called campylobacter) was discovered in 1980, it has been considered as a major cause in the pathogenesis of gastric ulcer, mucosa-associated lymphoid tissue (MALT) lymphomas, and gastric cancer. Eventually antibiotics were designed to eradicate this bacterium, which not only prevent peptic ulcer recurrence but also decrease the chances of developing gastric cancer. Around 50% of the world's human population is infected with Helicobacter pylori, a class I carcinogen. Eradication of H. pylori results in healing of gastric ulcer and may also reduce the incidence of gastric carcinoma. While various drug regimens have been used for the eradication of H. pylori such as triple or quadruple drug therapy, there has been an alarming increase in the resistance to antibiotics.
Helicobacter pylori can cause a chronic low-level inflammation of your stomach lining and is a major factor in the symptoms of acid reflux. Colonization of the human stomach by Helicobacter pylori and its role in causing gastric cancer is one of the richest examples of a complex relationship among human cells, microbes, and their environment. It is also a puzzle of enormous medical importance given the incidence and lethality of gastric cancer worldwide. There is a long felt but unsolved need to address GERD in a fashion that avoids the over administration of antibiotics, leading to increased antibiotic resistance.
Proton pump inhibitors (PPI's) work by blocking the production of acid in the stomach. In response, the body reacts by overcompensating, often revving up production of acid-making cells. Thus, one problem involved in attempting the cessation of PPI's is that individuals experience excess growth of acid producing cells in the stomach, so that when they unblock production of acid by stopping PPI doses, they have more of the acid-making cells, thus creating more acid production than they had previously experienced. The widespread treatment of GERD has also failed to reduce the incidence of esophageal cancers, with esophageal adenocarcinomas, which are associated with GERD, increasing by 350 percent since 1970. Thus, when people take PPI's, they do not cure the problem of reflux—but rather, they have just controlled the symptoms.
Stomach acid is needed to break down food and absorb nutrients, as well as for proper functioning of the gallbladder and pancreas. Taking PPI's changes the ecology of the gut and actually allows overgrowth of some things that normally would be kept under control. Long-term of use of PPI's may interfere with these processes and suppression of stomach acid, which kills bacteria and other microbes, may make people more susceptible to infections, like C. difficile, which can make one more susceptible to a dangerous infection marked by diarrhea, abdominal pain and even death.
C. difficile kills an estimated 14,000 to 30,000 people a year in the United States. Evidence of the link between C. difficile and PPIs was sufficiently strong that the Federal Drug Administration has issued alerts that PPI's may be causing a 65 percent increase in C. difficile-related diarrhea, that they may potentially lower magnesium levels—a condition that can cause muscle spasms, irregular heartbeat and seizures—and that they increase the risk of hip, wrist and spine fractures.
Clostridium difficile is a Gram-positive, strictly anaerobic, spore-forming bacterium found in mammalian intestinal tracts. C. difficile is one of the key public health problems in industrialized countries and one of the major nosocomial enteropathogens. C. difficile-associated diarrhea is currently the most frequently occurring nosocomial diarrhea worldwide. Two major risk factors for contracting C. difficile infections are the age of the individual and exposure to antibiotics. Antibiotic therapy causes alterations in the colonic microflora, allowing the development of C. difficile from preexisting or acquired spores. The pathogen synthesizes two major toxins, TcdA and TcdB, which glucosylate host GTPases, resulting in alterations in the enterocyte cytoskeleton. This induces intestinal cell lysis and inflammation, resulting in diarrhea, pseudomembranous colitis, and even death.
The long-term use of Prilosec and other proton-pump-inhibiting drugs is raising concerns as to the safety and wisdom of such long-term drug use as it invariably has consequences with respect to human health. PPI's are the third highest-selling class of drugs in the United States, with more than 100 million prescriptions and over $15 billion in sales. Some consider the long term use of proton pump inhibitors like Prevacid and Prilosec and the H2 blocker agents like Tagament, Pepcid, and Zantac to be dangerous. Such drugs significantly reduce the amount of acid available to digest food and the reduction of acid in the stomach also diminishes a primary defense mechanism for food borne infections, thus leading to an increased risk of risk of food poisoning.
Long-term use of PPI's can make it difficult to absorb some nutrients. Rebound acid hypersecretion, defined as an increase in gastric acid secretion above pre-treatment levels following antisecretory therapy, has been observed within two weeks after withdrawal of treatment and can lead to acid-related symptoms and possibly PPI dependency. Individuals have attempted to wean themselves off of these drugs gradually or else they experience a severe rebound of symptoms, often resulting in the problem being worse than it was before they started taking the medication. Emerging evidence suggests that PPIs are not as benign as once thought, with newer data implicating a potential association of PPIs with an increased risk of respiratory tract infections, gastrointestinal infections, bone fractures, hypomagnesemia, and the occurrence of rebound hyperacidity after discontinuation of PPI therapy.
In recent years, there have been numerous warnings about long-term use and high doses of PPI's being associated with an increased risk of bone fractures and infection with a bacterium called Clostridium difficile that can be especially dangerous to elderly patients. Studies have shown long-term PPI use may reduce the absorption of important nutrients, vitamins and minerals, including magnesium, calcium and vitamin B12, and might reduce the effectiveness of other medications, with the F.D.A. warning that taking Prilosec together with the anticlotting agent clopidogrel (Plavix) can weaken the protective effect (of clopidogrel) for heart patients. PPIH is the consequence of intestinal Mg2+ malabsorption. An underappreciated aspect of PPIH is frequent secondary electrolyte disturbances such as hypocalcemia and hypokalemia. The clinical significance of reduced calcium (Ca2+) levels is emphasized by several dozens of studies showing increased risk of bone fractures after chronic PPI use. Omeprazole inhibits passive paracellular Mg2+ fluxes, predominantly present in the small intestine and omeprazole directly interferes with important transcellular Mg2+ transport mechanisms of the colon.
The human gut harbors one of the most complex and abundant ecosystems colonized by more than 100 trillion microorganisms. Firmicutes and Bacteroidetes represent more than 90% of the relative abundance of the gut microbiome. The phylum Bacteroidetes is composed of Gram-negative, non-spore forming anaerobic bacteria that tolerate the presence of oxygen but cannot use it for growth. Actinobacteria (e.g., Bifidobacterium) are Gram-positive, multiple branching rods, non-motile, non-spore-forming, and anaerobic bacteria. The most abundant genera from the Bacteroidetes phylum are Bacteroides and Prevotella species. As the gut is an anaerobic environment, aerobic pathogenic species cannot invade and colonize it, but anaerobic and facultative pathogenic species can nevertheless invade it, causing diseases. High diversity defines healthy human gut microbiomes, whereas reduction in diversity is associated with dysbiosis—referring to an imbalance in the microbiome structure that results from an abnormal ratio of commensal and pathogenic bacterial species.
There is therefore a long felt but unsolved need for effective methods and compositions to reduce the likelihood of GERD and in treating, mitigating and preventing GERD, especially in concert with the widespread use of PPI's.